Infertility is a common problem throughout the world. Approximately fifteen percent of all couples encounter fertility problems during their reproductive lifetime and in about half of the cases the cause is of male origin (1-2). Despite the possible deleterious role of lifestyle, environmental and/or genetic factors evoked on male reproduction, the aetiologies of most infertility cases remain unknown. According to various sources, male factors represent about one third to 40% of all infertility situations. Routine semen analysis may indicate defective sperm production or diminished sperm motility as well as an abnormal sperm morphology resulting of a defective spermiogenesis. It may also reveal the absence of spermatozoa in semen, a situation termed azoospermia which concerns about 8% of men with fertility problems (3). It is the consequence of either an obstructed or discontinuous male genital tract such as the bilateral agenesis of the vas deferens (obstructive azoospermia; OA) or a failure of the testis to initiate or maintain spermatogenesis due to endogenous or exogenous abnormalities (non-obstructive azoospermia, NOA).
One of the most dramatic revolutions to occur in the field of assisted reproductive technology over the past two decades was the introduction of intracytoplasmic sperm injection (ICSI), which has indeed revolutionized the treatment of severe male infertility (4). For men with azoospermia, surgical retrieval of sperm cells from the epididymis or testicular biopsies in combination with ICSI opened new avenues in the management of male infertilities (5-7). In the vast majority of obstructive cases, spermatozoa are often abundant in the epididymis or seminiferous tubules, thus allowing high rates of retrieval through percutaneous epididymal sperm aspiration (PESA), microepididymal sperm aspiration (MESA) or testicular sperm aspiration (TESA) (8). However, in NOA subjects, the epididymis is devoid of spermatozoa and spermatogenesis is severely impacted or reduced. Regardless of the underlying aetiology, which often remains unexplained, restoring the fertility of NOA subjects generally relies on recovering spermatozoa from testicular biopsies via a sperm extraction procedure (testicular sperm extraction; TESE), which is then followed by in vitro fertilization with ICSI (9). Unfortunately, testicular spermatozoa are found in only around 50% to markedly lower rates of subjects with NOA (10). This poor result is due to the fact that both testes may be devoid of germ cells (i.e. Sertoli-Cell-Only syndrome; SCO), house an incomplete spermatogenesis (i.e. maturation arrest) or, under the best circumstance, contain only scarce residual sites of complete spermatogenesis. In the latter situation, spermatozoa can be retrieved by chance from a testis biopsy. This is the reason why counseling is crucial in the management of infertile men. None of the subjects parameters examined to date have been shown to predict successful biopsy/TESE outcomes (11).
Thus, it appears crucial for clinicians to identify factors that may predict a high probability of spermatozoa retrieval since unsuccessful sperm recovery procedures have significant emotional and financial implications. However, none of the examined parameters to date could be used to predict successful outcomes (11).
Apart from its obvious role in transporting male gametes, the seminal plasma provides a protective environment for ejaculated spermatozoa and improves their fertilization potential. Seminal plasma is a highly complex fluid, which contains proteins secreted from several glands in the male reproductive tract, including the testis, epididymis, seminal vesicles and prostate. Indeed, like most body fluids, seminal plasma contains many proteins at widely different concentrations, which renders scarce proteins very difficult to identify and quantify. Also, reproductive disorders can cause certain compositional changes that are known to alter the properties of seminal plasma. Thus, this bio fluid is considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. In addition, although its production may be altered, seminal plasma continues to be produced in most cases of infertility. Over the past decade, several studies have investigated the protein composition of seminal plasma in healthy donors and have identified numerous proteins through proteomic analyses (12). For example, a large-scale mass spectrometric analysis of human seminal plasma, conducted using an LTQ-FTICR instrument, allowed 923 seminal plasma proteins to be identified with high confidence (13). However, most previous studies have failed to identify known components of the seminal plasma, such as human beta-defensins (e.g, HBD1). This confirms that accessing the proteins present at very low concentrations is hampered by the overwhelming signals produced by a few dominant proteins. Indeed, thorough analysis of very complex biofluids requires an optimized strategy that is not exclusively based on mass spectrometry sensitivity and dynamic range.
However, there is a need to identify non-invasive technique and new methods for predicting the presence of reproductive cells in testis of an infertile or hypofertile subjects. In this way, it has been suggested that the characterization of new testicular germline biomarkers in the seminal plasma may be highly desirable.